目的:探究TLR10和BIRC5基因的易感性与甲状腺乳头状癌(PTC)的关系。方法:通过使用Agena Mass ARRAY平台对4个单核苷酸多态性(SNP)(rs11466653、rs11096956、rs11096955、rs9904341)进行检测评估,并采用卡方检验、遗传模型分析以及单体...目的:探究TLR10和BIRC5基因的易感性与甲状腺乳头状癌(PTC)的关系。方法:通过使用Agena Mass ARRAY平台对4个单核苷酸多态性(SNP)(rs11466653、rs11096956、rs11096955、rs9904341)进行检测评估,并采用卡方检验、遗传模型分析以及单体型分析等统计分析方法。结果:rs11096956位点(TLR10)的等位基因"C"与rs9904341位点(BIRC5)的等位基因"G"均与增加PTC的发病风险相关(rs11096956:OR=1.26,95%CI=1.09~1.97,P=0.031;rs9904341:OR=1.26,95%CI=1.17~2.04,P=0.019)。在遗传模型下,通过逻辑回归分析发现在共显性模型、显性模型以及加性模型中rs11096956 SNPs位点的多态性与增加PTC的发病风险相关。在共显性模型和显性模型下,rs9904341位点的多态性与PTC风险增加有关。此外,TLR10基因的SNPs位点构成的单倍体型"Trs11466653Trs11096956Crs11096955"与增加PTC的发病风险有关。分层分析显示,rs11096956(TLR10)和rs9904341(BIRC5)位点多态性可显著增加女性PTC的发病风险(P<0.05)。结论:发现表明rs11096956(TLR10)和rs9904341(BIRC5)的变异与PTC风险的增加有关,尤其是在女性人群中。展开更多
Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be asso...Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be associated with inflammatory diseases, such as infections, autoimmune diseases, and cancers. Meanwhile, TLR10, which can form heterodimers with TLR2, has been considered an orphan receptor without an exact function. The present study therefore aims to examine the effects of TLR2 and TLR10 on PI. Prostate samples and clinical data were obtained from the patients diagnosed with benign prostatic hyperplasia. The inflammatory cell model was established by adding lipopolysaccharide to RWPE-1 cells. Prostate tissues/cells were examined by histological, molecular, and biochemical approaches. Both TLR2 and TLR10 were found to be expressed in prostate tissues and RWPE-1 cells. mRNA/protein expression levels of TLR2 and TLR10 were both positively correlated with prostate tissue inflammatory grades. Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phosphonuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65), interleukin (IL)-6, and IL-8 than control cells. Moreover, HMGB1, phospho-NF-κB P65, IL-6, and IL-8 were down regulated after TLR2 knockdown and upregulated after TLR10 knockdown in RWPE-1 cells. TLR2 stimulation can activate the inflammatory signaling cascade in prostate epithelial cells. Conversely, TLR10 exhibited suppressive effects on inflammation. With antagonistic functions, both TLR2 and TLR10 were invoIved in PI. TLR10 could be a novel target in modulating inflammatory signal transduction of prostate epithelial cells.展开更多
文摘目的:探究TLR10和BIRC5基因的易感性与甲状腺乳头状癌(PTC)的关系。方法:通过使用Agena Mass ARRAY平台对4个单核苷酸多态性(SNP)(rs11466653、rs11096956、rs11096955、rs9904341)进行检测评估,并采用卡方检验、遗传模型分析以及单体型分析等统计分析方法。结果:rs11096956位点(TLR10)的等位基因"C"与rs9904341位点(BIRC5)的等位基因"G"均与增加PTC的发病风险相关(rs11096956:OR=1.26,95%CI=1.09~1.97,P=0.031;rs9904341:OR=1.26,95%CI=1.17~2.04,P=0.019)。在遗传模型下,通过逻辑回归分析发现在共显性模型、显性模型以及加性模型中rs11096956 SNPs位点的多态性与增加PTC的发病风险相关。在共显性模型和显性模型下,rs9904341位点的多态性与PTC风险增加有关。此外,TLR10基因的SNPs位点构成的单倍体型"Trs11466653Trs11096956Crs11096955"与增加PTC的发病风险有关。分层分析显示,rs11096956(TLR10)和rs9904341(BIRC5)位点多态性可显著增加女性PTC的发病风险(P<0.05)。结论:发现表明rs11096956(TLR10)和rs9904341(BIRC5)的变异与PTC风险的增加有关,尤其是在女性人群中。
基金the National Key Research and Development Program of China (Grant No. SQ2017YFSF090096)National Natural Science Foundation of China (Grant No. 81370855,81770756 and 81300627)+3 种基金Foundation of Science and Technology Department of Sichuan Province (Grant No. 2013SZ0006, 2015SZ0230, 2018JY0089 and 2017HH0063)1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (Grant No. ZY2016104)Youth Researcher Funding of Sichuan University (Grant No. 2017SCU11042 and 2017SCU04A17)Research Funding of Sichuan Health and Family Planning Commission (Grant No. 17PJ159,18PJ434 and 18PJ453).
文摘Prostate inflammation (PI) is closely related to the development and progression of chronic prostatic diseases: benign prostatic hyperplasia and prostate cancer. Toll-like receptor (TLR) 2 has been reported to be associated with inflammatory diseases, such as infections, autoimmune diseases, and cancers. Meanwhile, TLR10, which can form heterodimers with TLR2, has been considered an orphan receptor without an exact function. The present study therefore aims to examine the effects of TLR2 and TLR10 on PI. Prostate samples and clinical data were obtained from the patients diagnosed with benign prostatic hyperplasia. The inflammatory cell model was established by adding lipopolysaccharide to RWPE-1 cells. Prostate tissues/cells were examined by histological, molecular, and biochemical approaches. Both TLR2 and TLR10 were found to be expressed in prostate tissues and RWPE-1 cells. mRNA/protein expression levels of TLR2 and TLR10 were both positively correlated with prostate tissue inflammatory grades. Lipopolysaccharide-stimulated RWPE-1 cells expressed higher levels of TLR2, TLR10, high mobility group box 1 (HMGB1), phosphonuclear factor kappa-light-chain-enhancer of activated B-cells P65 (phospho-NF-κB P65), interleukin (IL)-6, and IL-8 than control cells. Moreover, HMGB1, phospho-NF-κB P65, IL-6, and IL-8 were down regulated after TLR2 knockdown and upregulated after TLR10 knockdown in RWPE-1 cells. TLR2 stimulation can activate the inflammatory signaling cascade in prostate epithelial cells. Conversely, TLR10 exhibited suppressive effects on inflammation. With antagonistic functions, both TLR2 and TLR10 were invoIved in PI. TLR10 could be a novel target in modulating inflammatory signal transduction of prostate epithelial cells.
基金supported by the National Natural Science Foundation of China(No.8212010801,82371699 and 82401977)the National Key Research and Development Project(No.2022YFC2704602 and 2022YFC2704502)the Major Project of Shanghai Municipal Education Commission's Scientific Research and Innovation Plan(No.2021-01-07-00-07-E00144)。
